Epigenetic Programming during thymic development sets the stage for optimal function in effector T cells via DNA demethylation
Teghanemt, A.; Pulipati, P.; Day, K.; Yorek, M. S.; Yi, R.; Misel, K. M.; Keen, H. L.; Au, C.; Maretzky, T.; Gurung, P.; Littman, D. R.; Issuree, P. D.
Show abstract
The repressive effect of DNA methylation at promoters is well-known. However, its role within conserved sequences in intragenic and intergenic regions is less clear. Using Cd4 as a model gene, here we show that DNA methylation regulates the function of stimulus-responsive regulatory elements in effector T cells. Two cis-elements orchestrate intra-and intergenic DNA demethylation of the Cd4 gene during thymic development, which in turn licenses a stimulus-responsive element, E4a, for its later function in effector cells. Deficiency in DNA demethylation leads to impaired E4a function, reduced H3K4me3 promoter levels and an inability to repel de novo DNA methylation during replication, ultimately leading to gene silencing. This physiological reduction in CD4 expression leads to a defect in Th1 polarization during cutaneous Leishmaniasis. Similar patterns of regulation were observed in a broad number of genes, highlighting an essential role for DNA demethylation during thymic development in modulating the function of stimulus-responsive elements.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Fam49b dampens TCR signal strength to regulate survival of positively selected thymocytes 97%
- Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2 96%
- Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection 95%
Similar papers in this journal
- T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling 95%
- Integration of Avidity and Differentiation is enabled by CD8+ T-cell sensing of IFN-γ 95%
- Gfi1 controls the formation of effector CD8 T cells during chronic infection and cancer 95%
Similar papers in this journal
- ILC1-derived IFN-gamma mediates cDC1-dependent host resistance against Toxoplasma gondii 95%
- Maternal schistosomiasis impairs offspring IL-4 production and B cell expansion 94%
- Biogenesis of P-TEFb in CD4+ T cells to reverse HIV latency is mediated by protein kinase C (PKC)-independent signaling pathways 94%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.